Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were undertaken to determine whether bovine lactoferrin (bLF) and related compounds, shown to prevent carcinogenesis in the colon and other organs in rats, have any toxic effects in long-term feeding studies. In experiment I, male F344/DuCrj rats received a basal diet containing 0.2% bLF for 40 weeks. No adverse findings were noted, furthermore, serum triglyceride level was significantly decreased to 72% of the control level, suggesting preventive effects against the metabolic syndrome. In experiment II, male and female F344/DuCrj rats were fed a basal diet containing 0.02, 0.2, 2.0 and 5.0% bLF, 2.0% bLF hydrolysate (bLF-H) or 0.1% lactoferricin (LFcin), a peptide derived from bLF, for 60 weeks in males and 65 weeks in females. No toxicological effects, including carcinogenicity, were evident in either sex. The results of the studies provide subjective support for safety of clinical studies of bLF for supplement use.
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PMID:Lack of chronic oral toxicity of chemopreventive bovine lactoferrin in F344/DuCrj rats. 1871 82

Gamma-tocopherol (gamma-T) alone or in combination with alpha-tocopherol has been shown to suppress biomarkers of oxidative stress in asthamatics and human subjects with metabolic syndrome. Oxidative stress has been implicated as a key event in prostate carcinogenesis. Hence, the purpose of this study was to examine the effects of gamma-tocopherol-enriched mixed tocopherol diet on prostate carcinogenesis in a murine prostate cancer model (TRAMP). 8 week old TRAMP males were fed 0.1% gamma-T-enriched mixed tocopherol diet that contained 20-fold higher levels of gamma-tocopherol, and roughly 3-fold higher levels of alpha-tocopherol. The effect of such diet on tumor and PIN development was observed. The expression of phase II detoxifying, antioxidant enzymes and Nrf2 mRNA and protein were determined by RT-PCR, immunohistochemistry and western blotting techniques. Treatment with gamma-T-enriched mixed tocopherols significantly suppressed the incidence of palpable tumor and Prostate Intraepithelial Neoplasia (PIN) development without affecting the expression of the transgene (SV-40). Tumor progression occurred with a significant suppression of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, heme-oxygenase-1 and phase II detoxifying enzymes. Treatment with gamma-T-enriched mixed tocopherol diet upregulated the expression of most detoxifying and antioxidant enzymes. Nrf2-a redox sensitive transcription factor known to mediate the expression of phase II detoxifying enzymes, was also significantly upregulated following treatment with gamma-T-enriched mixed tocopherol diet. Gamma-T-enriched mixed tocopherols significantly up-regulated the expression of Nrf2 and its related detoxifying and antioxidant enzymes thereby suppressing PIN and tumor development.
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PMID:Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice. 1911 3

The relationship of infertility, endocrinology and cancer has become clearer in recent years. Polycystic ovaries (PCO) increase the risk of endometrial cancer. Prolonged amenorrhoea, therefore, should be prevented in such cases with the use of cyclical progestogens, in order for regular withdrawal bleeds to be induced and the endometrium protected from long-term unopposed oestrogen stimulation. There is no secure evidence base on which a relationship between PCO and breast cancer can be based. No specific breast screening for women with PCO is, therefore, recommended. Hyperandrogenaemia and hyperinsulinaemia are conditions whose significance in terms of increasing both endometrial and breast cancer risks is increasingly recognised. The exact mechanism with which they influence carcinogenesis is still far from clear. Whether they act in isolation or as expressions of the common background of the metabolic syndrome - in interaction with other components of this syndrome - is still the subject of research.
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PMID:Anovulation with or without PCO, hyperandrogenaemia and hyperinsulinaemia as promoters of endometrial and breast cancer. 1926 56

Adiponectin is widely known as an adipocytokine with therapeutic potential for its markedly protective function in the pathogenesis of obesity-related disorders, metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. In the present study, we show that adiponectin inhibits adhesion, invasion and migration of breast cancer cells. Further analysis of the underlying molecular mechanisms revealed that adiponectin treatment increased AMP-activated protein kinase (AMPK) phosphorylation and activity as evident by increased phosphorylation of downstream target of AMPK, acetyl-coenzyme A carboxylase and inhibition of p70S6 kinase (S6K). Intriguingly, we discovered that adiponectin treatment increases the expression of tumor suppressor gene LKB1 in breast cancer cells. Overexpression of LKB1 in breast cancer cells further increased adiponectin-mediated phosphorylation of AMPK. Using isogenic LKB1 knockdown cell line pair, we found that LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, inhibition of adhesion, migration and invasion of breast cancer cells. Taken together these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. Our findings indicate the possibility of using adiponectin analogues to inhibit invasion and migration of breast cancer cells.
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PMID:LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. 1948 24

Diet and nutrition have played an important role in maintaining physiological homeostasis. Recent literature emphasizes potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic diseases driven by an inflammatory nidus. Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress induced injury which characterizes their pathogenesis. Patient control over diet and disease has been demonstrated in diabetes mellitus, cardiovascular disease, rheumatology, carcinogenesis and other diseases. Polyphenolic compounds are ubiquitous dietary components, mainly flavonoids and tannins. Specific polyphenols are effective in scavenging reactive oxygen and reactive nitrogen species. They are able to modulate genes associated with metabolism, stress defence, drug metabolizing enzymes, detoxification and transporter proteins. Their overall effect is protective in overcoming damaging effects of chronic diseases and in delaying the degenerative effects of ageing. The mechanisms involved in radical scavenging activity are complex, determined by the structure of the compound, redox status of the environment and interactions with other agents. Atherogenic dyslipidaemia associated with a pro-inflammatory pro-thrombotic state in metabolic syndrome and related risk of fatty liver, arthritis, neurodegenerative disorders and certain types of cancers are ideal therapeutic targets for bioactive phytochemicals which can combat oxidative stress induced damage at a sub-cellular level. It is relevant that purified micronutrients isolated from natural products may be less effective than a combination seen in the natural product due to synergistic effects of interacting agents. Some of these mechanisms and potential therapeutic targets are discussed.
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PMID:Relevance of nutritional antioxidants in metabolic syndrome, ageing and cancer: potential for therapeutic targeting. 1968 82

The metabolic syndrome and visceral obesity have an increasing prevalence and incidence in the general population. The actual prevalence of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES III, INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer. Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944,717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical significance and may have profound health benefits on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.
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PMID:Metabolic syndrome and risk of subsequent colorectal cancer. 1989 Oct 12

The incidence of hepatocellular carcinoma is rising due to alcohol drinking, hepatitis C viral infection and metabolic syndrome. Differential expression of CYP2E1 may play a pleiotropic role in the multistep process of liver carcinogenesis. Considerable attention has focused on the antitumor effect of trichostatin A (TSA) as well as CYP2E1 expression-induced apoptosis of cancer cells. However, very few studies have examined the mechanisms by which TSA has an antitumor effect and its association to CYP2E1 expression. The current study examined the action of TSA on CYP2E1 expression and the role of CYP2E1 in inducing apoptosis of HepG2 cells. Our data showed that TSA selectively induced CYP2E1 in four studied human hepatocellular carcinoma (HCC) cell lines (Huh7, PLC/PRF/5, Hep3B and HepG2), but not in normal primary human hepatocytes. TSA-mediated up-regulation of CYP2E1 expression was associated with histone H3 acetylation and the recruitment of HNF-1 and HNF-3beta to the CYP2E1 promoter in HepG2 cells. siRNA-mediated knockdown experiments showed that TSA-induced caspase-3 cleavage was decreased due to reduced expression of CYP2E1 in HepG2 cells. Moreover, down-regulation of CYP2E1 was accompanied by decreased production of mitochondrial reactive oxygen species. These results suggest that histone modification is involved in CYP2E1 gene expression and that CYP2E1-dependent mitochondrial oxidative stress plays a role in TSA-induced apoptosis.
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PMID:Histone modification-mediated CYP2E1 gene expression and apoptosis of HepG2 cells. 2040 16

Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options. Cancer research has largely focused on the molecular basis of oncogenic transformation and tumorigenesis for many years. Recent progress in cancer research has put the metastatic process at the center stage because higher metastatic potential of tumor cells is the major cause of mortality from solid tumors. Metastasis is a complex process that involves modulation of various molecular signaling networks. Tumor cells alter the microenvironment, attain greater cellular adhesion along with better ability to invade and migrate to gain access to circulation. These wandering tumor cells defy anoikis, survive in the circulation, exit into new permissive organ site and colonize distant organs. The microenvironment in which the tumor originates plays an important role in tumor initiation, progression and metastasis.
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PMID:Metastasis suppression by adiponectin: LKB1 rises up to the challenge. 2041 65

The increasing incidence of hepatocellular carcinoma (HCC) has led several countries to standardize and update its management. This review aims at summarizing these evolutions through six questions focusing on diagnosis and treatment. The radiological diagnosis of this tumor has been refined. Besides being hypervascular at the arterial phase, the "washout" in particular at the late phase of injection has become a prominent feature. Although routine ultrasound remains the corner stone of screening, contrast ultrasound has become a very reliable characterization tool as it allows continuous monitoring of the vascular kinetics. Biopsy of the tumor allows identification of conventional or molecular prognosis features, some of which could be used in current practice. The metabolic syndrome is an increasing etiology of HCC and carcinogenesis in this context may not always require the development of formal underlying cirrhosis. Associated (in particular cardiovascular) conditions account for an increased morbidity-mortality following surgery. Liver transplantation is the most effective treatment of early-stage tumors. The limited availability of grafts has led some countries including France to implement new allocation rules that are still evaluated and might need to be refined. Sorafenib is the first medical treatment shown to be effective in the treatment of HCC. This efficacy is however still limited and its indication is therefore restricted to Child-Pugh A, OMS 0-2 patients in whom a potentially curative treatment is contraindicated.
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PMID:Hepatocellular carcinoma--what's new? 2059 72

Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer.
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PMID:Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience. 2093 21


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